Nivolumab, Ipilimumab and Chemoradiation in Treating Patients With Resectable Gastric Cancer

April 10, 2026 updated by: M.D. Anderson Cancer Center

Pilot Study of Dual Checkpoint Inhibition Followed by Immuno-Chemoradiation in Patients With Resectable Gastric Adenocarcinoma (Concept ID 2016-NIV-0551)

This pilot phase I/II trial studies the side effects and how well nivolumab and ipilimumab in combination with chemotherapy and radiation therapy work in treating patients with gastric cancer that can be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Intensity-modulated radiation therapy uses thin beams of radiation of different strengths aimed at the tumor from many angles. This type of radiation therapy may reduce the damage to healthy tissue near the tumor. Giving nivolumab, ipilimumab, chemotherapy and radiation therapy may work better in treating patients with gastric cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicity profile of intravenous nivolumab in combination with ipilimumab after standard chemotherapy and followed by intravenous nivolumab in combination with fluoropyrimidine and intensity-modulated radiation therapy (IMRT) for the treatment of localized gastroesophageal junction (GEJ) and/or gastric cancer.

SECONDARY OBJECTIVES:

I. To assess the efficacy of double checkpoint inhibition (nivolumab + ipilimumab) followed by nivolumab plus chemoradiation.

II. To assess the overall safety and tolerability of adjuvant nivolumab in subjects with resected GEJ or gastric cancer.

III. To evaluate disease free survival (DFS).

IV. To explore changes in tumor stroma profile before and after immunotherapy and radiation therapy.

V. To bank tumor and blood specimen for future correlative analysis, including, but not limited to, biomarker analysis.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive oxaliplatin intravenously (IV) over 2 hours and fluorouracil IV over 48 hours on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment with nivolumab repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning course 4, patients also receive fluorouracil IV continuously for 5 days per week and undergo 25 fractions of IMRT for 5 weeks. Patients undergo surgical resection 5-7 weeks after completing radiation therapy.

Within 8-12 weeks post-surgery, patients with residual disease may receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 8 courses (16 weeks) then every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 84 days, every 12 weeks for 2 years, then every 6-12 months for up to 3 years.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
  • All subjects must have localized/eligible for surgery gastric cancer (GC) or GEJ carcinoma type III, with negative peritoneal washing. Subjects must have histologically confirmed predominant adenocarcinoma. The documentation of GEJ involvement can include biopsy, endoscopy, or imaging.
  • Subject must be previously untreated with systemic treatment (including HER 2 inhibitors) given as primary therapy for advanced or metastatic disease. No prior neoadjuvant chemotherapy, immunotherapy, radiotherapy and/or chemoradiotherapy are permitted.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  • Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days of treatment initiation).
  • Platelets >=100,000/mcL (within 28 days of treatment initiation).
  • Hemoglobin >= 9 g/dL or > 5.6 mmol/L; if patient is not actively bleeding and has hemoglobin of < 9g/dL, patient can receive blood transfusion to increase hemoglobin to >= 9g/dL (within 28 days of treatment initiation).
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCL]) > 60 mL/min for subjects with creatinine levels > 1.5 x institutional ULN (measured via 24-hour urine collection) (within 28 days of treatment initiation). Creatinine clearance should be calculated per institutional standard.
  • Serum total bilirubin =< 1.5 X ULN (1.5 mg/dL or 25.65 umol/L) OR direct bilirubin < ULN for subjects with total bilirubin levels < 1.5 X ULN. Except patients with Gilbert's disease (< 3 X ULN) (within 28 days of treatment initiation).
  • Aspartate aminotransferase AST (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR < 5 X ULN for subjects with liver metastases (within 28 days of treatment initiation).
  • Albumin >= 3 mg/dL (within 28 days of treatment initiation).
  • Prothrombin Time (PT) < 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time PTT is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin Time (aPTT) < 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 28 days of treatment initiation).
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug. Women must not be breastfeeding.
  • Prior to chemotherapy and immunotherapy, WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment (i.e. 30 days (duration of ovulatory cycle plus the time required for the investigational drug to undergo approximately five half-lives).
  • Males who are sexually active with WOCBP must agree to follow instructions for methods of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment (i.e. 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives). In addition, male subjects must be willing to refrain from sperm donation during this time.

Exclusion Criteria:

  • Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

    • NOTE: Testing for HIV must be performed at sites where mandated locally.
  • White blood cell (WBC) < 2000/uL.
  • Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g. hepatitis B surface antigen (HBsAg Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if hepatitis C virus- ribonucleic acid [HCV-RNA] negative).
  • History of allergy or hypersensitivity to study drug components.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • Patients with serious or uncontrolled medical disorders.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (chemotherapy, immunotherapy, IMRT)

INDUCTION CHEMOTHERAPY: Patients receive oxaliplatin IV over 2 hours and fluorouracil IV over 48 hours on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment with nivolumab repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning course 4, patients also receive fluorouracil IV continuously for 5 days per week and undergo 25 fractions of IMRT for 5 weeks. Patients undergo surgical resection 5-7 weeks after completing radiation therapy.

Within 8-12 weeks post-surgery, patients with residual disease may receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 8 courses (16 weeks) then every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
Drug: Fluorouracil
Given IV
Other Names:
  • 5-FU
  • 5-Fluracil
  • Fluracil
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
Drug: Oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • Ai Heng
  • Aiheng
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669
Procedure: Therapeutic Conventional Surgery
Undergo partial or total gastrectomy and lymphadenectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 30 days
The Bayesian method of Thall, Simon and Estey will be implemented for toxicity monitoring. Safety data will be summarized using frequency tables by organ system, grade and attribution for the neoadjuvant period and adjuvant period separately.
Up to 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rates
Time Frame: Up to 5 years
Response rates will be estimated along with the corresponding exact 95% confidence interval.
Up to 5 years
Incidence of adverse events in patients with resected gastroesophageal junction (GEJ) or gastric cancer
Time Frame: Up to 5 years
The Bayesian method of Thall, Simon and Estey will be implemented for toxicity monitoring. Safety data will be summarized using frequency tables by organ system, grade and attribution for the neoadjuvant period and adjuvant period separately.
Up to 5 years
Disease-free survival
Time Frame: From the date of surgery until disease relapse or death, whichever occurred first, assessed up to 5 years
Will be estimated using the method of Kaplan and Meier.
From the date of surgery until disease relapse or death, whichever occurred first, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Mariela Blum, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 7, 2019

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

December 12, 2018

First Submitted That Met QC Criteria

December 13, 2018

First Posted (Actual)

December 14, 2018

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-0012 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2018-02344 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Gastric Adenocarcinoma

Clinical Trials on Nivolumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Indonesia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe